A model of organ transplantation in inbred rats is being employed to determine which potential effector mechanisms in rejection are most important, and how it is that antibodies against antigens of the graft may in some cases promote long-term survival and function. We are studying the kidney as a graft because of ease in monitoring its functional state, and because of its relevance to a number of unsolved problems in clinical renal transplantation. We have established that the principal lesion in the Brown Norway to Lewis rat combination is an arterial and glomerular vasculitis, similar to that seen in large numbers of clinical rejections. A single dose of hyperimmune Lewis anti-BN serum to the Lewis recipient of a (Lewis x Brown Norway) F1 kidney produces long-term survival by abrogating the vasculitis without an apparent effect on the cellular response, although there is a 2 day delay in appearance of cytotoxic effector lympocytes (T cells) in recipient spleens. We are engaged in study of the prerequisites for such an enhancing antibody; so far, IgM is inactive, while IgG (IgGa plus IgGb plus IgGc) are very active. IgG may also recruit unsensitized B cell to become effector cells, and both B and T cells are modulated as effectors by intracellular cyclic nucleotide levels, cAMP and cGMP.